1. Field of the Invention
The present invention relates to a method and a device for atomizing (nebulising) a liquid, in particular a liquid medicament formulation, as well as a method for the production of such a device.
2. Description of Related Art
In the atomization of a liquid medicament formulation, the object is to convert, as much as possible, an accurately-defined amount of active constituent into an aerosol for inhalation. The aerosol should be characterized by a small mean value of the droplet size with a narrow droplet size distribution and by a small momentum (low propagation rate).
The expression “medicament formulation” used in the present invention is understood to include, apart from medicaments, also therapeutic agents or the like, in particular therefore all types of agents for inhalation. The present invention is however not restricted to the atomization of agents for inhalation, but in particular may also be employed for cosmetic agents or other liquids and possibly also for suspensions or the like, even if the following description is primarily directed to the preferred atomization of a medicament formulation for inhalation.
The term “aerosol” is understood in the context of the present invention to mean a preferably nebulous collection of a large number of droplets of the atomized liquid with preferably a substantially non-directed (random) and/or broad spatial distribution of the directions of movement and preferably with low velocities of the droplets.
International Patent Application Publications WO 92/04065 A1 (U.S. Pat. No. 5,178,138) and WO 03/047763 A1, European Patent Applications EP 0 471 323 A1 and EP 0 653 218 A1 and U.S. Pat. No. 5,241,954 disclose nebulisers for liquids for inhalation purposes. The liquid is, in each case, mixed with a gas stream and directed onto a deflecting surface to effect nebulisation. This is complicated and is not always effective, and in particular the droplet size may vary greatly.
International Patent Application Publication WO 92/19383 A1 discloses an atomization of a liquid without an additional gas stream or compressed air. A liquid jet is directed onto a conical deflecting surface for the atomization, so that the liquid is atomized in a plane transverse to the axis of the cone, in order to generate droplets with a diameter of less than 10 μm for inhalation purposes. It is difficult to generate an aerosol in this way having a defined droplet size and a narrow, constant droplet size distribution.
U.S. Pat. No. 5,261,949 relates to a method of producing an atomized liquid to be conveyed in a stream of a carrier gas and to an apparatus for implementing the method. A liquid mist for being conveyed by a carrier gas stream is produced from a liquid by atomizing the liquid into the carrier gas stream in the form a collection of droplets, deflecting the collection of droplets in the carrier gas stream at a deflection region, separating droplets in the collection of droplets which exceed a maximum size from the carrier gas stream, collecting at least a part of the separated droplets on at least one heatable contact surface, and at least partially vaporizing them into the carrier gas stream. This method requires a first aerosolization of the liquid in a spray of droplets and a second aerosolization of the larger droplets by means of the heatable contact surface. A further disadvantage is that a carrier gas stream is necessary. This makes it difficult or even impossible to generate an aerosol with the desired characteristics, in particular a low propagation rate. Moreover, the method is not suitable for inhalers to generate a defined aerosol of a medical formulation.
French Patent FR 2 682 049 A1 relates to a device for generating a mixture of air and vapor of hydrogen peroxide. The device comprises a nozzle for atomizing the liquid hydrogen peroxide pneumatically and generating a mixture of air and droplets of hydrogen peroxide. This aerosol is directed onto a contact surface heated to about 200° C. Thus, the droplets of hydrogen peroxide shall be vaporized so that vapor of hydrogen peroxide is generated.
UK Patent Application GB 2 214 088 A relates to a heated nebulizer system for producing a humidified and heated breathing gas to be inhaled by a patient undergoing inhalation therapy. Pressurized oxygen is discharged via a nozzle and generates an aerosol spray of liquid water and ambient air. This aerosol is directed in a conical pattern onto an annular heated surface upon which the aerosol impinges. The heated surface volatilizes at least a portion of the aerosol while allowing the remainder to coalesce and return through a port to a reservoir of the liquid water, Thus, it is desired to generated water vapor so that humidified and heated gas can be breathed.
UK Patent Application GB 744,547 A relates to a method for thermal production of an aerosol of an insecticide, such as DDT, bactericide or the like active material in which a solution or dispersion of the active material in a more volatile vehicle is caused to impinge onto a surface, heated to a temperature above the boiling point of the vehicle. As the result of the consequent rapid boiling of the vehicle, the latter assumes a state in which the bulk phase of the boiling material is separated from the hot surface by a layer of vapor of the vehicle. The liquid is discharged either between two heated plates or though a conduit surrounded by the heating jacket. This method is not suitable for generating a defined aerosol with the desired characteristics, in particular with low propagation rate and/or small particle size.
The Canon company markets under the model number “i850” a printer operating according to the so-called bubble jet principle. The printer comprises a plurality of nozzle openings with a diameter of 10 μm for ejecting ink droplets with a volume of 2 pl, i.e., with a diameter of about 12 μm. Liquid chambers in which the ink is vaporized by means of an electrothermal element are associated with the nozzle openings. The change in volume occurring on vaporization leads to the ejection of the ink droplets through the nozzle openings. In order to achieve the desired resolution of for example 4,800 dpi, the ink droplets are ejected at high velocity (10 m/sec or more) in a specific direction through a nozzle.
In the bubble jet principle, a complicating factor is that the ejection of the individual droplets and accordingly the renewed vaporization of ink have to be controlled individually for the individual nozzles, in order to achieve a desired print image. Apart from the timing, the site and momentum of the formed droplet are important in the bubble jet principle. For this reason, the print head comprises a plurality of individual heaters, ink chambers and nozzles, in which each configuration of heater, ink chamber and nozzle can generate and eject individual droplets only in succession. Such a print head is complicated and expensive to manufacture. A very large number of nozzles is required to achieve the droplet rate that is normally necessary for an inhaler. In addition there is the danger of the undetected stoppage or blockage of individual nozzles as well as the failure of individual heating elements, for example due to deposits or the like. Moreover, when the bubble jet principle is employed for medicament formulations further undesirable effects, such as a build-up of active constituent, reactions of the active constituent, or the like, may occur.